Physiology and Structure of the Small Airways in Patients With Chronic Airflow Obstruction or COVID-19 (PASSPORT)

The purpose of this research project is to study small airways physiological function in patients with chronic obstructive lung disease or COVID-19 and explore the relationship with in-vivo microanatomical small airway structure as measured by OCT. Correlating endobronchial assessment with multiple breath nitrogen washout and impulse oscillometry will allow the characterisation of the relationship between small airway structural findings and these validated investigations. A small volume lung wash, endobronchial brushings and the collection of a limited number of endobronchial cryobiopsy samples will be performed to better understand the endobronchial environment of the small airways through inflammatory studies. Following the completion of any such work, residual samples will be stored in a "bio-bank" to enable the completion of future work. Understanding the relationship with symptom-based quality of life scoring questionnaires and a functional assessment of exercise capacity will help elucidate the clinical impact of in-vivo small airways findings.

Study Overview

• Status: Unknown
• Conditions: COVID-19; Asthma; Copd; Small Airways Disease

• Study Type: Observational
• Enrollment (Anticipated): 42

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • The Royal Brompton
    • Contact: Christopher M Orton, MBBS; Phone Number: 8029 02073518029; Email: c.orton@rbht.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects over the age of 16 with either chronic airflow obstruction or COVID-19

Description

Inclusion Criteria:

1. Age 16 or over
2. Scheduled for bronchoscopy as part of clinical care or research protocol
3. No bleeding diathesis or therapeutic anticoagulation

4. COPD:

   • FEV1/FVC ratio <70% or

Asthma:

• Diagnosed by standard clinical methods
• Post-bronchodilator FEV1 ≥60% predicted or COVID-19 infection or previous COVID-19 infection (confirmed as per local guidelines)

Exclusion Criteria:

1. Unable to provide informed consent
2. Exacerbation of obstructive airways disease or respiratory infection requiring systemic antibiotics or corticosteroids in the 6 weeks prior to enrolment unless suffering from COVID-19 infection and bronchoscopy is required for clinical reasons

3. Contra-indications to performing lung function testing

   • Aortic aneurysm >6cm
   • Unstable cardiovascular disease (unstable angina, myocardial infarction or pulmonary embolism <4 weeks prior)
   • Severe aortic stenosis
   • Pneumothorax
   • Cerebral aneurysm
   • Thoracic or abdominal surgery <4 weeks prior

4. Contra-indications to passing oesophageal balloons

   • Oesophageal ulceration or varices
   • Sinusitis, recent nasal surgery or epistaxis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Chronic Airflow obstruction / COVID-19; Patients with either chronic airflow obstruction of COVID-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory resistance at 5Hz - 20Hz (R5-R20) (kPa/l/s) related to airtrapping as determined by quantitative CT (Expiratory phase low attenuation area <856 HU (%LAA <856 HU)	Impulse Oscillometry	Baseline, pre-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory reactance at 5Hz: X5 (kPa/l/s)	Impulse Oscillometry	Baseline, pre-procedure
Reactance area: Ax (kPa/l/s)	Impulse Oscillometry	Baseline, pre-procedure
Functional residual capacity by MBNW: FRCgas (L)	Multiple Breath Nitrogen Washout	Baseline, pre-procedure
Lung clearance index: LCI	Multiple Breath Nitrogen Washout	Baseline, pre-procedure
Ventilation heterogeneity conducting airways: Scond (L/s)	Multiple Breath Nitrogen Washout	Baseline, pre-procedure
Ventilation heterogeneity acinar airways: Sacin (L/s)	Multiple Breath Nitrogen Washout	Baseline, pre-procedure
Forced expiratory volume in 1 second: FEV1 (L)	Spirometry	Baseline, pre-procedure
Forced vital capacity: FVC (L)	Spirometry	Baseline, pre-procedure
Total lung capacity: TLC (L)	Plethysmography	Baseline, pre-procedure
Residual volume: RV (L)	Plethysmography	Baseline, pre-procedure
Functional residual capacity by plethysmography: FRCpleth (L)	plethysmography	Baseline, pre-procedure
Airway mean luminal diameter (Dmean)	Optical Coherence Tomography	Baseline, during the procedure
Airway inner lumen area (Ai)	Optical Coherence Tomography	Baseline, during the procedure
Airway wall area (Aw), airway wall percentage (Aw%) as determined by [Aw/(Ai + Aw) × 100%]	Optical Coherence Tomography	Baseline, during the procedure
Air trapping - expiratory phase low attenuation area <856 HU (%LAA <856 HU)	Quantitative CT	Baseline, pre-procedure
Modified MRC dyspnoea score	Patient reported outcome measure	Baseline, pre-procedure
St George's Respiratory Questionnaire Score	Patient reported outcome measure	Baseline, pre-procedure
Asthma-related Quality of Life Questionnaire (AQLQ) (if asthmatic)	Patient reported outcome measure	Baseline, pre-procedure
Asthma Control Questionnaire (ACQ) (if asthmatic)	Patient reported outcome measure	Baseline, pre-procedure
6-minute walk distance (m)	6-minute walk distance (m)	Baseline, pre-procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Inflammatory and pathological studies of airways brush, wash and cryobiopsy samples	Laboratory based scientific studies	Baseline, during the procedure

Collaborators and Investigators

• Sponsor: Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2019
• Primary Completion (Anticipated): August 22, 2021
• Study Completion (Anticipated): February 2, 2022

Study Registration Dates

• First Submitted: July 2, 2020
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 18, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Lung Diseases, Obstructive; COVID-19; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 18IC4688